The immune system’s complexity reared its head again at this conference as Dr. Montoya showcased some of the findings coming out of his large immune studies at Stanford. Montoya’s assertions that chronic fatigue syndrome (ME/CFS) is similar to systemic inflammatory response syndrome and should be called an inflammatory disorder were intriguing indeed. It’s still, however, hard understand what is going on in the immune system in ME/CFS.

This is a long blog; if you just want the main findings a quickie overview is given at the end of it.

IMMUNE SYSTEM

Montoya’s huge (584 person!) and impressive immune studies – the largest ever done in this disease – dominated several presentations. The studies are bit unusual in that they contained about twice as many healthy controls (n=392) as patients (n=192). Montoya posted an impressive list of 30 researchers he’s collaborating with at Stanford and elsewhere.

He spoke of a complex immune situation often characterized by both up and down immune activation, but which strongly suggested chronic fatigue syndrome is an inflammatory disorder.

Cytokine Study

Cytokines are molecules produced by immune cells that regulate immune functioning in many ways. Montoya tested many cytokines (51) but only two popped out in the first run of this study. That was surprising; large studies are particularly good at finding small but still significant differences, but this study found few differences between the ME/CFS patients and healthy controls than some smaller studies.

Lipkin and Hornig enhanced their cytokine study results by controlling for duration. The key for Montoya was severity. When he added severity to the picture, the immune findings popped out. In the more severely ill patients a rather eye-popping third of the 51 cytokines tested (leptin, CXCL-1, CXLC10, GM-SF, IFN-Y, GM-CSF, IL-4, IL-5, Il-7, IL-12p70, IL-13, IL-17F, NGF, TGF-b, CCLI, SCF and TGF-a) – most of them pro-inflammatory in nature – significantly increased.

Montoya proposed that TGF-b, traditionally thought of as anti-inflammatory, may have been acting as a pro-inflammatory cytokine. That cytokine has shown up in several ME/CFS studies before.

Interlude: Cytokine Results Still All Over the Map

The results were encouraging, but cytokine results in this disease are still all over the map. For years researchers have thought they MUST be involved in ME/CFS, but cytokine results have been stunningly inconsistent.

For example, while a 145 person Australian study did, like Montoya’s study, find increased levels of cytokines (IL-10, IFN-γ, TNF-α), none of those cytokines showed up in Montoya’s results.

A 99 person study from the Klimas group measuring 16 cytokines found significant alterations in 10 of them (increased – LT-a, IL-1a, IL-1b, IL-4, IL-5, IL-6, and IL-12; decreased – IL-8, IL-13 and IL-15.) IL-4/5-were increased in Montoya’s severe ME/CFS group, but IL-13 was decreased in the Klimas study and increased in Montoya’s.

Wyller’s recent large study of ME/CFS adolescents found no cytokine differences between those diagnosed with the Fukuda criteria cytokine and healthy controls. A Japanese/U.S. study found no evidence that either sleep deprivation or exercise effected cytokine levels as well.

The large Landi/Houghton 179 person study of longer duration patients found mostly cytokine reductions instead of increases (reduced levels of IL-7, IL-16, VEGF-a, CX3CLI, CXCL9; increased CCL24). If most of Montoya’s group were early-stage ME/CFS patients, that might help explain the differences, but we don’t know that they were. (Montoya did state that he is going to filter for illness duration.)

The Lipkin/Hornig cytokine study found increased levels of 16 cytokines in early or late duration patients vs healthy controls (IL-1a, IL-1ra, IL-4, IL-12p70, Il-13, CXCL8, TNFα, SFASL, CCL2, CCL3, CD40L, MCP1, TNFSF10, SCF, CFS1, and resistin). Only three of those (IL-12p70, Il-13, SCF) were found elevated in the Montoya study; thirteen were not.

An Australian study that tracked for severity in a different way from Montoya suggested that more severe patients do have higher cytokine levels. It found reductions in IL-1b, and increases in IL-7, IL-8 and IFN-y. Of those, IFN-y was increased in the Montoya study.

In a much (much) smaller cytokine study published earlier this year, Dr. Fletcher’s study suggested that dramatic shifts in immune functioning may occur over time. IL-a plays an important role in early ME/CFS and then declines. IL-8 levels were abnormally high early on but declined to lower than normal levels after a few years. Il-6 levels were low early on and elevated later. Ironically, the Montoya study didn’t find any of these cytokines elevated in his severely ill patients.

Conclusion (?)

Until cytokine results achieve more consistency they’re clearly not going to get traction in the medical world. The inconsistency seems surprising as most of these studies are from good labs. It’s possible, though, that subsets are mucking up the issue. Filtering for duration is clearly needed, and Montoya’s study suggested that filtering for severity is as well. The Klimas group’s Gulf War Syndrome study suggested that gender may need to be accounted for as well.

Dr. Peterson’s atypical patient subset may throw another loop into cytokine results. Peterson’s atypical ME/CFS subset group so dramatically affected cerebral spinal fluid results that it had to be excluded from the study altogether. Could this group be effecting blood cytokine results as well?

Researchers are not going to stop studying cytokines – they’re apparently too enticing – and it’s possible that studies underway may help us understand what is going on. If Lipkin/Hornig can, in their study underway, replicate their cytokine results in different duration patients – that will be something. Ditto with several good day bad day studies underway. If Montoya can duplicate the Lipkin/Hornig duration results that would really be something. Time will tell.

It’s also possible that cytokine levels per se aren’t as important as we might think. Broderick’s models suggest that context is key; in the right context a factor can be important even if it’s levels are not raised. His models suggest that treatments targeting just two cytokines might be able to enable ME/CFS patients to exercise again. (See upcoming IACFS/ME treatment blog).

Montoya’s network analysis indicated that Il-1B – an important regulatory cytokine associated with increased pain – was the most important factor 24 hours after exercise. That certainly makes sense given what we know about exercise and pain.

Another possibility is that cytokines in the nervous system are more important than those in the peripheral blood. It’s thought, for instance, that cytokines must contribute to central sensitivity syndromes (CSS’s) such as fibromyalgia as well, but a similar issue with consistency apparently applies there. Staud has suggested that cytokines probably play a major in CSS, but only within the central nervous system.

No Biomarker Yet – An immune signature that shows up only in the more severely ill gives us clues about the illness but obviously isn’t going to work as a biomarker. But what would happen if Montoya essentially shoved those people into a more severe state by having them exercise? Would adding exercise to the mix make the more moderately ill patients look like more severely ill patients?

Montoya’s Exercise Study

Would exercise make moderately ill ME/CFS patients in the throes of post-exertional malaise look like severely ill patients? The answer to that question was no.

Montoya’s maximal exercise test produced opposite results from the cytokine study done in patients at rest. This time, exercise reduced the levels of four cytokines (TNF-a, IL-8, CCL4, ICAM-1) while increasing the levels of only 1 (CXCL-10).

Both TNF-a and IL-8 increase during exercise in healthy people, however. The fact that both went down in ME/CFS patients may be notable. If immune exhaustion is present then perhaps one might expect cytokine levels to drop when the body is faced with an exercise stressor.

A 2014 review of exercise studies reported that while exercise does appear to effect the complement system and gene expression and increase oxidative stress in ME/CFS, it does not appear to effect cytokines. Montoya’s results suggested the opposite.

At the Stanford Symposium, Montoya announced that the gene expression results indicated that ME/CFS was similar to a disease called systemic inflammatory response syndrome or SIRS. He repeated that assertion again; this time stating that ME/CFS was a “100% match” to SIRS. (The abstract was a bit more cautious, stating that the gene expression results were “very similar” to it and similar diseases).

SIRS has been called a“cytokine storm”

The concept of SIRS came out of ten years of work at a Toronto trauma lab by Dr. William Nelson. SIRS is a kind of cytokine “storm” – a term sometimes used in ME/CFS – which refers to a positive feedback cycle that results in higher and higher levels of cytokines. SIRS also effects both pro and anti-inflammatory cytokine levels as well.

SIRS refers to a state of systemic inflammation after infection or some other insult and can result in organ dysfunction and failure. Intriguingly, given the Australian metabolomic group’s suggestion that the metabolomic results in ME/CFS are similar to sepsis, it’s closely related to sepsis.

SIRS has other manifestations that some may find familiar. Increased heart rates, lower or higher than normal body temperatures, rapid breathing rates, and low white blood cell counts found in SIRS have also been found in ME/CFS. The rapid breathing rates, by the way, are associated with either increased metabolic stress due to infection or inflammation or may signal inadequate perfusion because of the onset of anaerobic cellular metabolism.

Other possible links include fibrin deposition, platelet aggregation, and coagulopathies aka Dr. Berg’s findings in ME/CFS some years ago. Dr. Montoya’s immense gene expression study almost couldn’t have uncovered a more interesting disease to link to ME/CFS. How serendipitous as well – if this all turns out – that Ron Davis and some members of his Open Medicine Foundation team have done an enormous amount of work on sepsis.

How is SIRS treated? In some ways (blood volume enhancement, anti-anaphylaxis drugs, selenium, glutamine, eicosapentaenoic acid, and antioxidants) that can be helpful in ME/CFS.

Epigenetic Modifications Point at Immune System and HPA Axis

Montoya’s epigenetic study suggested an infection (or some other insult) had indeed occurred in ME/CFS. Greatly increased rate of methylation in ME/CFS patients’ immune regulatory genes suggested some infection or other environmental insult had occurred.

Other epigenetic modifications were found to affect HPA axis genes. Given the strong interaction between the HPA axis and the immune system, it wouldn’t be surprising at all to find that some event had tweaked both the HPA axis and immune genes in many ME/CFS patients. (The Montoya group is currently engaged in a promising HPA axis study.)

Other gene groups affected by methylation (epigenetic modification) include genes that play a role in, yes, metabolism. One gene highlighted in a whole genome polymorphism study has been implicated in lactic acidosis (NUFS7). A polymorphism in this gene, which transfers electrons from NADH to CoQ10, could result in increased oxidative stress and reduced mitochondrial output.

Is Chronic Fatigue Syndrome an Inflammatory Disease?

Finding increased immune activation in severe ME/CFS patients, and with gene expression results a close match to SIRS, Montoya asserted that ME/CFS is an overactive immune disease and proposed that its new name should include the word “inflammatory.” Montoya results suggest this, but it’s hard to see how any consensus can be reached until we get more consistent results from the cytokine studies (???).

Pathogens

When asked about retroviruses, Montoya suggested there was no cheese down that tunnel. In several of his newsletters Montoya promised “exciting” new findings regarding pathogens but none were presented at this conference.

Allergy Study Reveals Intriguing Subset

Dr. Levine’s allergy study was, for me, one of the surprise highlights of the conference. This nice big study demonstrated how valuable a resource the multi-site ME/CFS experts centers are, and how valuable a tightly integrated network of research centers will be.

In one of the bigger ME/CFS studies to date, Levine queried 200 patients in five sites regarding the incidence of allergic symptoms/conditions and found that the presence of sinusitis and hives distinguished ME/CFS patients from healthy controls. (My guess is that the presence of sinusitis is overlooked and understudied in ME/CFS).

An allergy subset appears to have increased pain sensitization as well

The fact that having either of those conditions resulted in patients experiencing more pain suggested that an immune process was ramping up their pain levels. That hypothesis was strengthened when Levine found that this group also had a much, much higher incidence of migraine, tension headaches, back pain, neck pain, and fibromyalgia. Plus they had more gut and inflammatory symptoms. Something clearly appeared to be driving a pain sensitization process in these patients.

What is the tie that binds these findings together? Levine suggested it might be mast cell activation. Plus, Dr. Levine noted that both mast cells and neurons secrete two factors: nerve growth factor and substance P, known to increase pain. Then there’s tryptase to consider. A recent study suggested that modification of a tryptase gene could be behind some cases of EDS, POTS, IBS, ME/CFS and FM. Another suggested mast cell activation may be occurring in ME/CFS

This is the kind of study that makes you wonder why the heck it hasn’t been done before. The study was surely not expensive, yet it might illuminate much about ME/CFS. It was funded by the Hitchens Foundation.

The idea that an important immune enzyme called RNase L had been broken into pieces and was not only no longer working properly but was actually causing channelopathies and other issues raised a great deal of interest in ME/CFS the 2000’s. At some point work on the enzyme stopped but RNase L was not forgotten.

In a surprise a Spanish group looked for and found the broken-up bits of the enzyme in fibromyalgia. The results were too variable for the 37 dKA form of the enzyme to be considered a biomarker but they did suggest that a subset of FM patients carried it.

Even more surprising was their finding of another broken up bit of RNase L (70 kDa) which was almost totally associated with the FM patients (p<.0001). They’ve create custom-made antibody to identify it and will apparently keep working on it.

PATHOGENS

POSTER: EBV Rides Again

We’ve heard so much about EBV over the years that we forget what a special virus it is. It’s’ true that almost everyone has been infected with EBV, and most have no problem with it, but EBV is no walkover.

When one is exposed to EBV later in life, it causes infectious mononucleosis (glandular fever) and is associated with several forms of cancer (Hodgkin’s lymphoma, Burkitt’s lymphoma, gastric cancer, nasopharyngeal carcinoma, central nervous system lymphomas). Evidence suggests that EBV infections result in a higher risk of many autoimmune diseases including dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and multiple sclerosis. Lastly, while hardly mentioned in the medical world (ME/CFS is not even mentioned in the Wikipedia article) but foremost in ME/CFS patients minds, EBV is a well-known trigger of ME/CFS.

EBV must have a multitude of tricks up its sleeve to contribute to so many illnesses. The idea that it plays a major role in ME/CFS has risen and fallen over the years. Right now, that idea seems to be more in its descendant phase, but as Dr. Klimas’s study shows, it ain’t over until it’s over; EBV may still very much figure in this disease.

Micro RNA’s – small bits of RNA – regulate which genes get expressed. It turns out that EBV, tricky virus that it is, encodes viral miRNA’s of its own. (EBV was the first virus found able to do this. Given the immense amount of EBV research being done (over 25 studies published in November alone) that was perhaps no surprise.)

HHV-6 appears to contribute to symptoms in ME/CFS

Peripheral blood mononuclear cells (PBMCs) were collected from ME/CFS patients and healthy controls before, during and after exercise, and various tests were done to assess EBV miRNA’s. Preliminary results suggested that ME/CFS patients’ cells express higher levels of EBV proteins than normal and thus might be more likely to support EBV reactivation.

Plus some strange features emerged. The immune cells in ME/CFS tended to be smaller and have less volume (Ron Davis has found something similar). Instead of forming a classic “pump” shape the ME/CFS nuclei take on a puckered and wrinkled look as if they were aged. Plus, when a key immune transcription factor called STAT I gets activated, presumably by the virus, it ends up in the wrong part of the cell – a pattern indicative of viral reactivation.

All of this suggests that EBV may be tweaking ME/CFS cells in strange ways and that the virus may still play a part in ME/CFS.

POSTER: A Better HHV-6 Test

It’s clear that herpesvirus tests leave something to be desired and Nancy Klimas’ group is attempting to find a way to improve the diagnostic effectiveness of the Elisa test. The current test are provide only yes-infected or no-not infected answers and are particularly unreliable at the high and low ends of the spectrum.

This study, involving Dr. Govindan from Tufts University and four Florida researchers, used various statistical tests to see if they could develop a truly “quantitative” Elisa for HHV-6.

The intercept they developed allowed them to accurately stratify patients, and showed that the HHV-6 intercept they produced was negatively associated with physical functioning; i.e. the higher the intercept – the worse the ME/CFS patients physical functioning was. This suggested that a) HHV-6 does contribute to the symptom burden in ME/CFS, and b) that this new test could aid doctors in determining when to apply antiviral therapies.

POSTER: Enterovirus Brain Infection Found

Dr. Chia’s work to get the medical world to take enterovirus infections in ME/CFS seriously continues. He gave a workshop on enteroviruses and seemed to be in demand; every time I saw him he was engaged in conversation with a group of people.

His poster highlighted the possible effects of enteroviruses in the most dramatic way. It told the story of a young man who first developed gut problems and then severe ME/CFS. Tests for herpesviruses were normal, but his Echovirus antibody levels were sky-high. Stomach and colon biopsies stained positive for enteroviruses but enterovirus RNA was not detected in his blood (it often isn’t).

Unfortunately, the young man failed to respond to either alpha or gamma interferon or to SSRI’s, benzodiazepines or acid suppressants. Repeated MRI’s of his brain and spinal chord were normal. Six years into his illness, at the age of 29, he committed suicide.

His ending was tragic, but his story was not over. His harvested brain provided clues as to what may have happened. Neither a brain culture nor an RT-PCR picked up signs of enterovirus, but a western blot found protein bands which were similar to those found in the young man’s stomach biopsies (but different from those found in tuberculosis and lymphoma).

Dr. Chia concluded that this finding replicated a similar finding dating back to 1994. He concluded that the

“finding of viral protein and RNA in the brain specimens ….is consistent with a chronic, persistent infection of the brain causing debilitating symptoms. EV is clearly one of the causes of ME/CFS, and antiviral therapy should be developed for chronic EV infection.”

Like herpesviruses, most enteroviral infections are passed off quickly, but like herpesviruses, enteroviruses are also associated with serious disorders including polio, meningitis, myocarditis, hand, foot and mouth disease and others. According to Wikipedia, treatment for enterovirus infections is primitive, consisting mostly of relieving symptoms such as pain as they occur.

One hopes at some point an independent lab will take up Dr. Chia’s work and give it the replication it needs and he deserves.

Conclusions

The cytokine findings are disappointingly inconsistent, but the immune system is a vast place and gene expression, epigenetic modeling and other studies continue to point a finger at it. The Montoya studies should tell us much, plus the entry of noted researchers such as Ian Lipkin and Mady Hornig, Maureen Hanson, Derya Unutmaz, Michael Houghton and Patrick McGowan into the field ensure that we’ll be learning much more about the immune system in the years ahead.

Marshall-Gradisnik’s NCNED team is churning out immune studies at a rapid rate, Broderick’s early modeling studies suggest an immune focused 1-2 punch may knock out post-exertional malaise, and Fluge and Mella are testing another autoimmune drug, cyclophosphamide, in clinical trials.

Both Fluge/Ron Davis believe an immune process may be targeting energy production in our cells, the same may be true for ion channels, and it’s now clear that an autoimmune process is producing POTS in some patients. Every microbiome study thus far suggests altered microbial diversity and/or gut leakage into the blood could be sparking an immune response.

The Simmaron Foundation’s expanded spinal fluid study should give us a better handle on what’s happening in the brain just as new techniques to measure the amount of neuroinflammation present in the brain come online.

Finally, it’s encouraging that researchers are getting serious about subsets – and finding them when they look for them.

Major Findings

Increased levels of pro-inflammatory cytokines are associated with increased severity in ME/CFS;

Exercise, on the other hand, appears to down-regulate cytokine levels in ME/CFS including several cytokines that are typically increased during exercise in healthy people;

Gene expression results suggest ME/CFS is very similar to a sepsis-like condition called systemic inflammatory response syndrome (SIRS) which shares some other characteristics with ME/CFS;

Epigenetic modifications suggest that events may have altered the expression of genes involved in both the HPA axis and immune systems in ME/CFS;

One subset of ME/CFS with sinusitis and/or hives also falls prey to other pain sensitization type disorders such as migraine, fibromyalgia, headache and back pain. Mast cells could be implicated;

A broken up form of RNase L, an important enzyme involved in fighting pathogens, showed up in fibromyalgia;

Beca

Exactly, Mimi. Shoemaker, Brewer or some other mycotoxin expert may already have research findings or theories published on this. Probably no reason for a mycotoxin/cytokine link not to be playing a part in this thousand-name, same results illness. Who was it that said about 35% or more of the people who came into the practice had positive mycotoxin test results? Was it Dr. Klimas, and how would we find out the correct information without having an appointment? Data, anyone?

Cort Johnson

I don’t see why not… I would think that very different pathogens produce different immune responses. I’m reminded of Simmaron’ insect vector illness study. Nobody until now has assessed whether mosquito and tick borne illness are present in a subset of ME/CFS. If they are I wouldn’t surprised if we see at least a somewhat different immune profile showing up in those patients.

Kim_

Rose

Cort – have you ever written an article on the locale of where most of these cases are cropping up? Similar to what happened at Incline Village? I ask this because I saw a map of where tick-borne illnesses were found. Many were in the northern states – NY NJ CT and some in CA. It would be interesting to find out.

marta

“no cheese down that tunnel” if i had been drinking something i would have snorted it out of my nose with laughter! thanks for making me laugh! also thanks for all this information. i can see myself in bits and pieces of it– can’t wait until more is known-close to 35 years now……sigh.

Audrey Scougall

Yes 40 years now, the first 25 were the worst. Now food and chemical siensitivity reduced,but need to stay in the right environment. Someone said that ME/CFS is like the end stages of HIV, well the end stages of HIV AIDs involves systemic Candidiasis and Candida was a major part of my illness and treatment.with 7 years continuous Nyatatin and Nizoral. Still essenetial to be on a low carbohydrate diet,. Leaky gut & leaky skin, food macro-molecules circulating in the blldstream, severe hvies that almost sent me insane, bloating, acidosis and exhaustion soon comes back. Yes, fungal and yeast is a major part of this illness. Why does it get such sparce attention?

Cort Johnson

I think it’s really the lack of money. I think that Dr. Levine’s study was the kind of study that would be done in many diseases as a matter of fact. The more money we have, the more investigators we have – the more we get the kinds of studies that look at all aspects of ME/CFS including candida and hives and I’m sure many others. We desperately need these studies to ferret out the subsets in this illness.

Michael Walzer

All I know is I am very very grateful to have had the expertise of The Klimas Clinic, Dr Peterson, And Dr Lerner. In addition the Vanderbilt University all showing almost all of the finding mentioned in the IACFSME -Part II series. I became illl in 2006 with sudden angioedema, hives, and locked fingers = (Most probably a severe Mast Cell Attack in hindsight. I was put on high doses of prednisone 40mg for 3 months to control (hives, inflammation, fatigue improperly long by a local allergist.)

In high school I developed severe mono- hospitalized for 2 weeks = EBV. As years went by I found on my own hunt that while my blood was negative gluten sensitivity – a fecal test showed a transglutaminase autoimmune reaction, gluten and casein intolerance through fecal testing – most accurate. = Leaky gut for sure. I quickly developed PEM, cognitive dysfunction with significant recall issues and lack of reading stamina. I tested positive for active EBV, Cocksackie viruses, HHV6 B (the one not associated w MS). Low NK cells, totally disjointed cytokines and 90% TNFA.

I had a spinal tap that showed high pressure, no serotonin in fluid, went on Immuovir in the earlier years and did well in the short term (clearly not placebo – but then developed significant joint pain.) I was fiven a strong antibiotic to wipe out some bacteria I can’t remember the name of.. I was told I was a malingerer by one of our own.

I went on Cidofovir IV for 8 months to pound down an active HHV6 and EBV. Only the HHV6 was quelled . The EBV remained lower but persistently active. I was then switched to high dose Valcyclovir for another 6 months to no avail…Dr Lerner didn’t believe in immune modulators like LDN – so Iknew it was time to move on. He was a great doctor and he treated me with kind respect.

I moved on to other Me/CFS specialist. I had constant constipation.. I was switched to famvir and immune supplements.. I then developed syncopy and was tied to my bed. I have always been anemic, and failed VO2 max studies when I was healthier. A sharp ME specialist suspected possible MCAS, in addition to my diagnosed/failed tilt table. Zaditen turned my syncope into manageable POTs w tachycardia. I developed severe skin hives months after, diarrhea with food ingestion – clinical MCAS. Vanderbilt diagnosed Hyper – Adrenergic POTS. A skin, gut, colon biopsy w CD117 confirmed MCAS.

On an aside my daughter 12 was diagnosed asI was with gluten and casein intolerance and recovered from pallor, gut, headache, and profound fatigue. Fortunately, she has not been exposed I hope to EBV or too much stress at her tender age.

I am still awaiting the results of my gut biopsy that was sent to Dr Chia for analysis for Cocksackie virus.

While I am blessed to have the means to afford the the medical care and access to great ME/CFS specialist. I am still astounded that not 1 ME/CFS specialist has thought to ask me to be part of a serious clinical investigation??? The above certainly isn’t about me but rather what might be discovered by someone like myself with 10 years of history of severe ME/CFS and other cross over illnesses, a daughter potentially vulnerable to the beginning of this horrid illness and why my bloood, genes, etc aren’t being cynically investigated for the benefit of the rest of the community not as fortunate as I have been?

I hope I am approached because i believe my history could help both clinicians, researchers, and most importantly other sick patients. maybe there are enough of us with all these anomalies that its not necessary? I hope that is the case. I harbor no resentment just have an interest in helping out fellow patients, clinicians, and researchers.. So if you there is a researcher interested I am available. If we have enough subjects than please ignore this reply. Sincerely and with great hope for our future health..

Cort Johnson

My goodness Michael – what a story you have! I sincerely hope that both you and your daughter get in a study soon. I believe bot the Bateman Horne Center and the Simmaron Research Foundation are doing genetic studies and I know the Simmaron Research Foundation study is looking for patients with effected family members. I don’t know if its still open or not but I will pass your info onto the lead investigator.

I would hope, by the way, that the network of research centers to be created by the NIH will enable more patients like you to get into more research studies.

Great article, Cort! The more I read about inflammation, the more eye opening it becomes as to its all encompassing destruction going on in our bodies. I believe it’s why many of us go through faulty body temperature issues perhaps. I also believe we’re dealing with pathogens here… Including mycotoxins and viruses, metals, bacteria and even vaccines, but at low lying levels that aren’t being detected in the mainstream. I’ve been getting treatment for pathogens… Detected over 60 so far. Treating and eradicating and retesting. It seems like there’s no one simple answer and to me that suggests its the body in overwhelm due to many issues compounding. But what do I know? Lol

Rose

Alyssa – can you share which pathogens you were diagnosed with? Were they from a mosquito or tick-bite? How did they treat it – with antibiotics? I’d appreciate any information. A family member has symptoms that doctors have not discovered the cause. They didn’t do intensive blood testing. Who would you go to for blood testing for mycoplasmas and such?? Thx

DeborahRNBSN

Let us remember Cort
Johnson at Christmas
and donate to his paypal
account. Many of us
would not be where we
are in our illness, nor
would we know we
have done everything
in our power at this
time to get well.

Cort Johnson

Thanks so much Deborah! Health Rising actually has a donation drive coming up very shortly. Please remember Simmaron as well; they’re doing great work and they have been soooo supportive of me and Health Rising.

JEANIE

it’s not all about mycotoxins people, theres more to mold exposure than that! do some research on mold voc’s for example, understand that many mold byproducts cause mast cell activation along with many other chemicals,toxins,allergens,irritants, gasses,fumes,toxic nanosized particles ,ect. and a sick building without any mold can be very harmful too, your work place, inside, outside, the dose makes the poison your not looking at the big picture, you have to stop with the mind set that its one thing and realize that with environmental exposures that harm it can be multiple chemical,toxins,allergens,irritants, chronic exposure is a key word, chronic exposure means chronic mast cell activation , mast cells degranulate when in contact with mold and spill toxic contents causeing secondary poisoning and even if they don’t degranulate they realease toxins to try to deal with the agent at hand, the airways are seceptable to damage and organs can become leacky, infection can than accur and you can be seceptable to many infectious agents at this point and when it goes systemic BBB breaks down, meningitis can accur, and you can have a lot of damage through the sinus/olfactory , brain pathways as well. seems to me that finally a lot of of may end up on the same page, environmental exposures !!!!! I’ve been trying to get this reconized for a long time. and now that it finally may all the good work Obama put in place to help us may be undone by the one who doesn’t believe in global warming, he threatens to undo it all! don’t let it happen just because you may not understand or realize that a environmental exposure may very well be the cause of your illness, the beginning of the process that caused you to end up with this disease cause truth is all of this should have been known and reconized a long time ago and we don’t have time to waist now.

Audrey Scougall

Yes, good comment. in the 1980s we called it Allergic to the 20th Century, it is still true, but plus the additional challenges in the 21st, Mast cells amongst other things, produce histamine, body stress produces cortisol, Immune dysfunction, it is hypersensitised, on fast forward and red alert to many different substances, medications, antibiotics, insecticies, moulds, chemicals, food macro-molecules, cigarette and wood smoke, you name it. We are hyper-sensitised, the advance wsrning system for the world, like the canaries down the coal mine.The immune system on red alert? No wonder we have adrenal crashes! ‘They should have known it long ago?’ yes, I’m sure they did and do know it now, but we are just collateral damage on the way to making a fortune. Governments and big business do not spend a lot of money on something they already know.Climate change? Human physiology change? yes it is all happening. Knowing minute changes in cytokines or the mitochondria or any other reductionist information will not reduce the onslaught sustained in this modern life. True we DON’T HAVE TIME TO WASTE NOW, but money talks, especially where, how and for what it is available.

JEANIE

Thank You Cort! that actually makes me fell pretty good, I’m not the greatest at functioning so for me to push myself to do this research (as you probably know) has been very hard and oh how I wish I could be better at organization! I’m very happy to see that both environmental exposures and mast cells are finally getting the attn. they deserve!

weyland

It’s important to note that Dr. Chia’s work is itself a replication of the earlier British work, so persistent enterovirus infection as a cause of ME is already a replicated finding. Very few of his findings are unique. Other researchers need to acknowledge not just the existence of this evidence, but the nature of it as well and what it tells us. Instead, the evidence is either ignored (NIH post-infectious study) or misunderstood (OMF big data study, Lipkin plasma study, etc). You will not find the virus in the blood, and not finding it there does not refute any of the existing evidence. And even if the virus was there in the blood to find via PCR assay, this is in ignorance of the evidence showing that persistent enteroviruses can undergo terminal deletion of the 5′ end of the viral genome (Chapman et al.) or might be a novel sequence that differs from wildtype virus (Galbraith et al.) and thus the PCR primers being used might fail to detect the virus depending on what they’re targeted at.

weyland

No, his gut findings are not new as far as I recall. The enterovirus VP1 antibody that Chia uses (5-D8/1) was developed in the UK in the 1980s by James Mowbray and Galal Yousef. While they never published distinctly on finding chronic infection of the gut, it is mentioned in passing in one of Mowbray’s papers I believe. He presumed that the gut was chronically infected because he was well aware of the tropism of the virus and was able to recover persistent virus in the stool, but his main focus was on finding the viral protein in the blood, which he was quite successful at.

Carollynn

Per many visits with Chia, viruses might be quite active and still not found in blood because they are embedded in tissues and nerves. For me, Chia has found enterovirus embedded in the tissue RNA of biopsies after endoscopy and sinus surgery. He talks about the connection between the stomach/gut and brain via the vagus nerve. The only way to know if it’s in the vagus nerve or brain is autopsy. Chia also talks about how, once it’s in the brain, it can travel anywhere via the nerves. this would of course be true of other pathogens as ell.

Rose

I know you’re not a doc Cort, but you research probably more than most. What is the takeaway here? Should people begin taking herbal antibiotics? I know omega 3 has anti-inflammatory properties. Does anyone else know what the strongest ones are?

Carollynn

Be cautious with anti-inflammatories. They can turn on viruses, especially those in the hopers family. I believe that being on statin drugs–powerful TNF-a blockers–are what caused me to become sick with ME a few years after I’d seemed to recover from EBV mono. While I went off the statins a year later, I have not regained my health. Later, other TNF-a blocking drugs in the steroid family, prescription retinol for my face and Flonase or Nasonex for sinuses, caused me to have shingles on my face, in my nose, and in my eyes. In time I learned about many natural substances that also have TNF-a blocking actions that are equally problematic for me. While some are very helped by these drugs and supplements, and others not. If herpes viruses are part of your profile, I urge special caution.

Rose

Thanks for sharing that Carolyn. I’ve never heard that before. I’ve always read inflammation is something to fight. I suppose any interaction in the body is possible. I wish the government would put more money into finding answers to real problems rather than the mating habits of flies.

Carollynn

I’m writing something more in-depth about the anti-inflammatories that I hope to share soon, hopefully by early Jan.. Inflammation is not all bad; at the right time and p;lace, it’s an essential part of a healthy immune response. To counter inflammation at that point can invite pathogens further in instead of dealing with them more definitively. At other times inflammation is harmful. It can be so problematic because at any one time our body might be responding to an invader with “good” inflammation and over-staying its welcome with unhelpful inflammation in another part of the body, but to tamp it down in one place means tamping it down systemically and perhaps hurt us somewhere else. I may be an extreme of that, but perhaps I’m representative of a subset that would be important to know.

Rose

December 3, 2016 at 1:46 am -

It’s interesting – I grasp what you’re saying, but it does seem it would be a tricky issue to address. I’ll look for what you write.

Carollynn

December 3, 2016 at 3:18 am -

That is exactly the motivation I need to do it, Rose! Thanks!

Rose

December 3, 2016 at 5:29 am -

Certainly!

DeborahRNBSN

December 4, 2016 at 6:15 pm -

Let us not forget to remember
Cort Johnson during the holiday
season through donations to PayPal
on Health Rising and by putting
Amazon Smile
in search bar on Amazon
and choosing Health Rising.
Many of us would not be where
we are in our disease by making
informed decisions nor would we
have peace over the fact that we
have done all that is possible.

TK

The allegy study is the most interesting to me. The fact that patients with allergy suffered higher symptom level tells me that CFS people are sensitive to inflammation. That’s consistent with my experience with flu shot that knocks me out for 2 weeks.

At the end, it may not be inflammation or the immune system. Rather, it could be the brain’s sensitivity to the inflammation that causes the constant fatigue and ache, and then sickness after exercise.

Melee

Dr Stephen Fry in Arizona very specifically rejects the International Consensus Criteria & the Canadian Consensus Criteria. When I moved to AZ I wanted desperately to find a physician here who would not laugh me out of his office or instruct me to go directly to a psychologist b/c the symptoms I was describing weren’t a real illness, and that maybe I should get up off my lazy butt and exercise (6 doctors did this before I gave up). When I found Dr. Fry I was thrilled, but the woman answering the phone soon became hostile to my questions (e.g., “Does Dr. Fry subscribe to the ICC or the CCC?” and “what are his thoughts on the chronic sepsis theory?”). She did ask him, and he instructed her to tell me he absolutely does not accept the ICC or CCC, and that if I want more answers I will have to pay for a consult. I would stay far away from Dr. Stephen Fry in Arizona – he is not TRUE ME/CFS friendly – probably another snake-oil salesman, from what I’ve learned personally, and from what I can find online.

abridged

Here’s a conundrum — all my doctors start looking for answers in the same place: inflammation. But all the standard infl markers (c-reactive protein, ana, etc) are always normal. What does it mean when inflammation is seen as a major component of all illnesses, but then someone who is ill shows no infl? Are there tests which would reflect infl levels differently?
(Diagnosed with CFS 2yrs)

Cort Johnson

Chris Duran

A simple mechanism should be considered to explain why inflammation could/does cause ME/CFS–that inflammation causes Upper Airway Resistance Syndrome. I am not referring to the improper definition of UARS where it’s called “mild sleep apnea”, but rather the accurate one that describes arousal from deep sleep to lighter stages due to labored breathing.

More specifically, swelling at the epiglottis, vocal folds or other lower airway areas creates resistance to breathing (not cessation) when the parasympathetic nervous system is most active (i.e., during sleep).

B) The airway constriction is manageable for the person in all but the deepest stage 4/Slow Wave Sleep; during this stage, the body becomes too relaxed to subconsciously maintain the airways, and the person is aroused to a lighter stage of sleep

So, has anybody considered that nearly impossible to observe airway constrictions during Stage 4/Slow Wave Sleep is the direct cause of the fatigue-related symptoms of ME/CFS?

It seems obvious to me, in hindsight, after nearly ten years of troubleshooting my CFS as if it were the transient swelling in my airways that I knew it was–only to finally be diagnosed with chronic enterovirus and HHV-5 infections. None of five endoscopic exams found the issue, and none of the four sleep doctors and studies yielded a conclusion for why I was missing Stage 4/Slow Wave Sleep.

Chris

As possibly one small piece of the puzzle–I suggest that the major symptoms of CFS are actually caused immediately by a condition called Upper Airway Resistance Syndrome (UARS).

With inflammation around the epiglottis (from any source), one struggles to breathe during sleep. It’s relatively easy to diagnose if it’s persistent and the sleep specialist is looking for it, but if it only happens at maximum swelling and is transient, then it is very easily missed. This would roughly align with the study that showed that something like 70% of FM sufferers have undiagnosed UARS (what if most of the other 30% just weren’t adequately diagnosed???)

The key is that at the moment a person attempts to enter slow wave/deep sleep, their parasympathetic nervous system is at its most active, and thus any vasodilation (swelling) is too. Plus, during deep sleep the muscles in the body (including throat near epiglottis) are at their most relaxed.

Therefore–what if only during this specific moment at the onset of deep sleep does a person have an airway restriction? This is known to manifest as arousing out of deep sleep and into a lighter stage of sleep, yet remaining asleep, and is distinct from the sleep apnea with which it’s commonly confused.

Proposed Conclusion: Regardless of the cause of the inflammation, perhaps the fatigue felt by CFS sufferers is most directly caused by transient UARS, in turned caused by inflammation in the throat that’s nearly impossible to detect unless one is observing that point of constriction at the exact right moment?

One can get 8 hours of lighter sleep and still feel extremely fatigued without deep sleep. Many people get sleep studies that show poor deep sleep, but it seems to be treated as simply correlated with CFS rather than a cause. Lastly, chronic sinusitis could be another cause of UARS and can be essentially an extension of inflammation in the lower airway (i.e., throat), and it’s prevalence in CFS could be an indicator that there are underdiagnosed lower airway restrictions in sufferers. I had to see four ENTs and four sleep doctors (and four sleep studies) before any of them pinpointed this as the immediate source of my fatigue problem–so I wouldn’t be surprised if neurologists and other CFS specialists would miss this cause too.

Chris

Daniel

Hi All, I just want to ask if anyone ever tried using medical cannabis as an alternative meds? I have read many articles about medical marijuana and how it can help you in terms of chronic pain, bone injuries, eating disorder/anorexia, anxiety disorders and panic attacks, inflammation, even cancer and a lot more. Like this article about a marijuana strain from:http://www.ilovegrowingmarijuana.com/sour-power/ . Cbd and thc are also new to me and I don’t even smoke. If this is true I cant find any solid conclusive evidence that speaks to its efficacy. Any personal experience or testimonial would be highly appreciated. Thanks

Cort Johnson

rentre

Alternative medicine are more accepted now a days due to it’s promising results unlike pharmaceutical medicine, alternative medicine don’t give negative effect such as kidney and liver problems when it comes to long term use. As for my alternative medicine usage, I use medical marijuana. Different strain has a variety of uses and effect depending on your needs. Visit this https://www.gyo.green/holy-smoke-seeds-strawberry-diesel-dojo-smo-sdd-f.html